Mitral valve is the structure that seperates left atrium and left ventricle in the heart. Our lab has been focusing on the mechaism of mitral valve prolapse (MVP) from a developmental perspective. MVP affects 2.4% of the population and results in more than 7,000 open heart surgeries each year in the US. MVP is characterized by excessive cardiac mitral valve tissue growth resulting in prolapse, impaired valve closure and mitral regurgitation (MR). Serious complications resulting from valve dysfunction can result including endocarditis and congestive heart failure. Familial
studies by our group and others have demonstrated that MVP can manifest during childhood, suggesting that genetic abnormalities expressed during valve development become exacerbated over a lifetime.
Causes of MVP remain poorly understood. However, we recently reported data from two approaches that have made significant inroads into understanding the genetics and etiology of MVP.
First, we identified loss of function mutations in the cell polarity gene, DCHS1 in three families with inherited MVP. Additionally genetic studies identified mutations in another gene, DZIP1 as segregating with MVP in multiple families.
Pathway analyses of genome wide variants combined with the discovery of DCHS1 and DZIP1 mutations led to the hypothesis that primary cilia are a unifying pathway regulating mitral valve structure and function. Primary cilia are solitary cellular protrusions that function as “antennae”. Our finding that primary cilia are primarily observed during development, further supported the new paradigm that MVP is a developmentally based disease that progressively gets worse with age.